title: Effects of calorie restriction and IGF-1 receptor blockade on the progression of 22Rv1 prostate cancer xenografts.
abstract: Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile.
authors.affiliation: Department of Urology, School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA. cogalet@gmail.com.
authors.forename: Colette
authors.initials: C
authors.lastname: Galet
authors.forename: Ashley
authors.initials: A
authors.lastname: Gray
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Said
authors.forename: Brandon
authors.initials: B
authors.lastname: Castor
authors.forename: Junxiang
authors.initials: J
authors.lastname: Wan
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Beltran
authors.forename: Franck J
authors.initials: FJ
authors.lastname: Calzone
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.forename: William J
authors.initials: WJ
authors.lastname: Aronson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D031204:Caloric Restriction; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; C000597236:IGF1R protein, human; D009363:Neoplasm Proteins; D017451:Receptors, Somatomedin; C545764:ganitumab; D017526:Receptor, IGF Type 1